Diazabicyclo Analogues of Maraviroc: Synthesis, Modeling, NMR Studies and Antiviral Activity

Overview

Journal Medchemcomm

Publisher Royal Society of Chemistry

Specialty Chemistry

Date 2018 Aug 16

PMID 30108760

Authors

L Legnani

D Colombo

A Venuti

C Pastori

L Lopalco

L Toma

M Mori

G Grazioso

S Villa

Affiliations

Soon will be listed here.

Abstract

Two diazabicyclo analogues of maraviroc, in which the azabicyclooctane moiety is replaced by diazabicyclooctane or diazabicyclononane, were synthesized and tested, through a viral neutralization assay, on a panel of six pseudoviruses. The diazabicyclooctane derivative maintained a significant infectivity reduction power, whereas the diazabicyclononane was less effective. Biological data were rationalized through a computational study that allowed the conformational preferences of the compounds to be determined and a correlation between the inhibitory activity, the bridge length of the bicycle, and the rotational barrier around dihedral angle to be hypothesized. A high-field NMR analysis supported the modeling results.

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